OBJECTIVES To examine the influence of cytokines on the release of soluble mediators in the peripheral blood and intrathecal compartments. RESULTS Cytokines, such as interleukin-1 (IL-1), are potent stimulators of endogenous cytokine release and the neuroendocrine axis, and thus play an important role in the communication between the immune system and the brain. We have been investigating the influence of IL-1 on other cytokines, such as interleukin-6, in the peripheral blood and intrathecal compartments. Following our demonstration that IL-6 is released endogenously from within the CNS, we have been investigating the primary cellular source. This research has focused on the endothelial cells of the blood-brain-barrier. In addition, we have been investigating the degree to which corticosteroids are involved in modulating these proinflammatory responses, which has bearing on the role of steroids in sepsis and anaphylactic shock. FUTURE DIRECTIONS Our studies are now focused on endothelial cells of the blood-brain-barrier. For this project, we have established endothelial cell cultures that will permit the research to go forward with in vitro models of the BBB. KEY WORDS cytokines, interleukin-1, interleukin-6 cerebrospinal fluid, psychoneuroimmunology FUNDING NIMH Dissertation Award, NSF Predoctoral fellowship, NIMH MH41659 PUBLICATIONS Reyes, T.M. and Coe, C.L. 1998. The proinflammatory cytokine network Interactions in the CNS and blood of rhesus monkeys. American Journal of Physiology 43 R139-149. Reyes, T.M. & Coe, C.L. 1998. Resistance of the central nervous system interleukin-6 to glucocorticoid inhibition in monkeys. American Journal of Physiology 44 R612-618.